Method for Treating Vulnerable Plaque

ABSTRACT

A method for treating a vulnerable plaque associated with a blood vessel of a patient is disclosed. The method includes positioning an electrical lead adjacent a vulnerable plaque lesion, and then delivering at least one electrical pulse to the lesion.

RELATED APPLICATION

This application claims priority to U.S. application Ser. No. 10/835,798as a continuation application, and that application claimed priority toU.S. Provisional Application No. 60/467,005, “Method for TreatingVulnerable Plaque” to Maura G. Donovan, filed Apr. 30, 2003, theentirety of each of which is incorporated herein by reference.

TECHNICAL FIELD OF THE INVENTION

The present invention relates generally to the field of vasculartherapies. More particularly, the invention relates to a method andsystem for treating a vulnerable plaque associated with a blood vesselof a patient.

BACKGROUND OF THE INVENTION

Heart disease, specifically coronary artery disease, is a major cause ofdeath, disability, and healthcare expense. Until recently, most heartdisease was considered primarily the result of a progressive increase ofhard plaque in the coronary arteries. This atherosclerotic diseaseprocess of hard plaques leads to a critical narrowing (stenosis) of theaffected coronary artery and produces anginal syndromes, known commonlyas chest pain. The progression of the narrowing reduces blood flow,triggering the formation of a blood clot. The clot may choke off theflow of oxygen rich blood (ischemia) to heart muscles, causing a heartattack. Alternatively, the clot may break off and lodge in another organvessel such as the brain resulting in a thrombotic stroke.

Within the past decade, evidence has emerged expanding the paradigm ofatherosclerosis, coronary artery disease, and heart attacks. While thebuild up of hard plaque may produce angina and severe ischemia in thecoronary arteries, new clinical data now suggests that the rupture ofsometimes non-occlusive, vulnerable plaques causes the vast majority ofheart attacks. The rate is estimated as high as 60-80 percent. In manyinstances vulnerable plaques do not impinge on the vessel lumen, rather,much like an abscess they are ingrained under the arterial wall. Forthis reason, conventional angiography or fluoroscopy techniques areunlikely to detect the vulnerable plaque. Due to the difficultyassociated with their detection and because angina is not typicallyproduced, vulnerable plaques may be more dangerous than other plaquesthat cause pain.

Atherosclerotic plaques vulnerable to rupture are typically smalldeposits covered by thin fibrous caps (less than 70 microns) coveringlipid cores. Within the fibrous cap is a dense infiltrate of smoothmuscle cells, macrophages and lymphocytes. Many believe the lipid poolis formed by pathological process involving low-density lipoprotein(LDL), macrophages, and the inflammatory process. The macrophagesoxidize the LDL, producing foam cells. The macrophages, foam cells, andsmooth muscle cells sit beneath the endothelium and release varioustoxic substances, such as tumor necrosis factor and tissue factor. Thesesubstances damage the arterial wall and surrounding areas and can resultin generalized cell necrosis and apoptosis, pro-coagulation, andweakening of the fibrous cap. The inflammation process may weaken thefibrous cap to the extent that sufficient mechanical stress, such asthat produced by increased blood pressure, may result in rupture. Thelipid core and other contents of the vulnerable plaque (emboli) may thenspill into the blood stream thereby initiating a clotting cascade. Thecascade produces a blood clot (thrombosis) that potentially results in aheart attack and/or stroke. The process is exacerbated due to therelease of collagen and other plaque components (e.g., tissue factor),which enhance clotting upon their release.

Several strategies have been developed for the detection (e.g.,diagnosis and localization) of vulnerable plaques. One strategy involvesthe measurement of temperature within a blood vessel. For example,vulnerable plaque tissue temperature is generally elevated compared tohealthy vascular tissue. Measurement of this temperature discrepancy mayallow detection of the vulnerable plaque.

Another detection strategy involves labeling vulnerable plaque with amarker. The marker substance may be specific for a component and/orcharacteristic of the vulnerable plaque. For example, the marker mayhave an affinity for the vulnerable plaque, more so than for healthytissue. Detection of the marker may thus allow detection of thevulnerable plaque. Alternatively, the marker may not necessarily have anaffinity for the vulnerable plaque, but will simply change propertieswhile associated with the vulnerable plaque. The property change may bedetected and thus allow detection of the vulnerable plaque.

Regardless of the strategy used for detection, a formidable problemremains in the treatment of the vulnerable plaque. Without appropriatetreatment, the vulnerable plaque may rupture and subsequently releaseembolic material and cause great risk to the patient, especially whenthe patient is not in a clinical setting. Drug and other therapies existthat may reduce the size and chance of vulnerable plaque rupture over arelatively long time frame. Percutaneous transluminal coronaryangioplasty (PTCA), which is commonly used to treat hard plaques, iscontraindicated. In the PTCA procedure, a catheter having an inflatableballoon at its distal end is introduced into the coronary artery, andthe balloon is inflated to flatten the hard plaque against the arterialwall. Inflation of a balloon catheter near a vulnerable plaque lesioncould rupture the thin fibrous cap that covers the lipid pool, resultingin precisely the clotting cascade that treatment would seek to prevent.

Thickening of the inner wall of a vessel is clearly an unwanted anddeleterious side effect when treating hard plaques. However, suchthickening could have a positive effect when it serves to strengthen thethin fibrous cap found atop a vulnerable plaque lesion. With the lesionthus stabilized, time is provided for the use of statin drugs or otheragents to shrink or remove the lipid pool. These therapies, however, maynot be desirable or effective for all patients, including those havingvulnerable plaques on the immediate verge of rupture. With suchtherapies, accidental or unanticipated rupture of these truly vulnerableplaques may occur in a non-clinical setting. Therefore, it would bedesirable to provide a treatment strategy that would provide relativelyimmediate treatment of the vulnerable plaque within a clinical setting.Furthermore, it would be desirable for such a treatment strategy toprevent any embolic material from escaping and causing risk to thepatient.

Accordingly, it would be desirable to provide a strategy for treatingvulnerable plaque that would overcome the aforementioned and otherdisadvantages.

SUMMARY OF THE INVENTION

One aspect of the invention provides a method of treating a vulnerableplaque associated with a blood vessel of a patient. The method includespositioning an electrical lead adjacent a vulnerable plaque lesion, anddelivering at least one electrical pulse from the electrical lead to thelesion.

Another aspect of the invention provides a method for treating avulnerable plaque lesion. The method comprises directing an electricalpulse toward a vulnerable plaque lesion for a sufficient time period tothicken a fibrous cap.

An additional aspect of the invention provides a method for treating avulnerable plaque lesion. This embodiment provides directing anelectrical pulse toward a vulnerable plaque lesion for a sufficient timeperiod to stimulate increased capillary growth near the lesion.

The foregoing and other features and advantages of the invention willbecome further apparent from the following detailed description of thepresently preferred embodiments, read in conjunction with theaccompanying drawings. The detailed description and drawings are merelyillustrative of the invention, rather than limiting the scope of theinvention being defined by the appended claims and equivalents thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flow chart of a method of treating a vulnerable plaqueassociated with a blood vessel of a patient, in accordance with oneembodiment of the present invention;

FIG. 2 is a flow chart of a method of treating a vulnerable plaquelesion, in accordance with another embodiment of the present invention;and

FIGS. 3A, 3B, and 3C are illustrations of one embodiment of a device fortreating a vulnerable plaque lesion in accordance with one embodiment ofthe invention.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

FIG. 1 illustrates a flowchart depicting the first embodiment of amethod in accordance with the instant invention. Method 100 begins atblock 110 where an electrical lead is positioned adjacent a vulnerableplaque lesion.

In the following description, vulnerable plaque treatment is describedin the context of a catheterization detection and treatment procedurefor a patient. The vulnerable plaque may be treated in a clinicalsetting thereby allowing for controlled treatment in an environment inwhich immediate care is given. Treating the vulnerable plaque in amanner according to the present invention may prevent the accidental orunanticipated release of emboli in a non-clinical setting. As such,complications stemming from vulnerable plaque rupture, such as heartattack and stroke, may be avoided. It should be noted that the terms“detect” and derivatives thereof, when used in regard to vulnerableplaque, refer to the diagnosis and localization of the lesion

Prior to positioning the electrical lead, it may be desirable topredetermine one or more treatment sites including vulnerable plaque.This aspect of the invention is shown in FIG. 2, as block 210. Thetreatment site(s) may be located during a vulnerable plaque diagnosticprocedure. Numerous such detection procedures are known in the art andmay be adapted for use with the present invention. The strategiesinclude, but are not limited to, temperature detection strategies,labeling strategies, imaging strategies, general strategies fordiscriminating the vulnerable plaque from surround healthy vasculartissue, and the like.

The temperature detection strategies may include a comparison of thetemperature of various portions of a blood vessel. The temperature ofthe vulnerable plaque is typically one or more degrees Celsius higherthan healthy vascular tissue because of increased metabolic activity(i.e., inflammation). For example, a relatively normal blood vesseltemperature may be about 37° C. whereas the vulnerable plaque may have alocalized temperature as high as 40° C. As such, the temperature-sensingdevice may be used to detect vulnerable plaque(s). Numerous devices forsensing temperature are known in the art. By way of example, thetemperature-sensing device may be a thermography catheter analogous tothat described in U.S. Pat. No. 6,245,026 to Campbell et al. and U.S.Pat. No. 6,475,159 to Casscells et al. As another example, a guidewireincluding thermal sensors and any number of other devices known in theart may be used for sensing vessel temperature and detecting thevulnerable plaque.

Other detection strategies may utilize any number of properties specificto a vulnerable plaque for detection. For example, vulnerable plaquesgenerally include a localized concentration of specific lipids,proteins, and factors. Measurement of these components may facilitatedetection. The detection may be achieved and/or enhanced by labeling.For example, the vulnerable plaque may be labeled with an antibodymarker specific for a plaque component wherein the antibody may includea radiolabel. The radiolabel may then be detected with an appropriatedetection device known in the art.

The vulnerable plaque may be detected endovascularly as with, forexample, a catheter based platform. By way of example, the endovasculardevice may be a light treatment catheter analogous to that described inU.S. Pat. No. 6,475,210 to Phelps et al. Alternatively, the vulnerableplaque may be detected from external the blood vessel. For example, adevice for detecting the vulnerable plaque may be positioned through anincision in the patient. The device may then detect the vulnerableplaque without the need for catheterization. During such a procedure,detection may be achieved during open surgery or in a minimally invasivemanner. As another example, the vulnerable plaque may be detectedexternal to the patient, such as with an imaging device (e.g., devicesutilizing magnetic resonance, ultrasound, infra-red, fluorescence,visible light, radio waves, x-ray, etc.). Those skilled in the art willrecognize that the strategy for detecting the vulnerable plaque may varyfrom the described methods. Numerous methods and devices for thedetection of vulnerable plaque may be adapted for use with the presentinvention.

The vulnerable plaque diagnostic procedure may be performed in aprevious procedure distinct from treatment or, alternatively, as acommon medical procedure. Furthermore, to practice the instantinvention, the diagnostic procedure need not detect the precise locationof the vulnerable plaque(s). The treatment procedure of the presentinvention may be employed in vascular region(s) merely suspected ofincluding vulnerable plaque (i.e., a prophylactic-type treatment). Forexample, a patient determined to have an elevated risk of vulnerableplaque may undergo a treatment strategy in accordance with the presentinvention, and especially the embodiment depicted in FIG. 1, at variousregion(s) generally known to include such plaques.

After the lesion has been located, positioning the electrical lead nextrequires accessing a target area. Numerous methods may used to accessthe target area. In some embodiments of the invention, a catheter-basedsystem will be used to position the electrical lead. Catheter-basedsystems are well known in the art, and generally comprise a catheterthat is guided to the target area using a guidewire. The catheter isslidably attached to the guidewire via a lumen in the body of thecatheter, such that the catheter surrounds the guidewire lumen, andslides along the guidewire. Such systems are generally monitored foraccurate placement with imaging technologies, such as fluoroscopy, andmay comprise the use of radio-opaque dyes. Catheter-based systems mayinclude other devices as well, and may include the detection means asdescribed above.

Other delivery systems may also be used. In another embodiment of theinstant invention, the lead may be positioned through a thoracotomy. Ina thoracotomy, an opening is created in the thoracic area of a body. Useof a thoracotomy for positioning the lead may prove advantageous forpositioning the lead in certain positions within the thoracic region. Ina thoracotomy placement of the electrical lead, a thoracotomy is made toprovide access to the target area, and the electrical lead is placed inthe desired position after passing through the thoracotomy.

Another embodiment of the instant invention includes using alaparoscopic approach to positioning the electrical lead. Laparoscopy isa surgical technique that uses a series of smaller incisions, largeenough to allow insertion of a light, and appropriate surgical tools.Although laparoscopy is less invasive than a thoracotomy, it may notalways be preferred to use a laparoscopic approach. In a laparoscopicplacement of the electrical lead, appropriate incisions are made toprovide access to the target area, and the electrical lead is threadedthrough the incisions and placed in the desired position.

Yet another embodiment of the instant invention comprises the use ofopen surgical techniques to position the electrical lead. Although thisis perhaps the most invasive technique, it may be preferred for locatingthe electrical lead in certain positions.

The lead may be positioned at any appropriate location to deliver the atleast one electrical pulse. One embodiment comprises locating the leaddirectly within a blood vessel. Such an embodiment is likely to entailuse of a catheter-based system. The electrical lead may be placeddirectly in the blood vessel that comprises the vulnerable plaquelesion, such that no vessel wall is in the path of the electricalpulses. In another embodiment of the invention, the electrical lead maybe placed in a blood vessel that is not the same blood vessel thatcomprises the vulnerable plaque. In such an embodiment, at least twovessel walls will be in the path of the electrical pulse—the vessel wallcontaining the electrical lead, and the vessel wall comprising thevulnerable plaque lesion.

In another embodiment, the electrical lead is positioned epicardially.In an epicardial placement, the electrical lead is placed in anepicardial position, adjacent the heart. The placement may be performedendovascularly, or may be positioned with a thoracotomy, laparoscopictechniques, or open surgical techniques. Placement of a differentelectrical device is disclosed in U.S. Pat. No. 5,716,379, issued Feb.10, 1998 to Bourgeois et. al., which is assigned to the same assignee asthis application. FIG. 1 of the '379 patent illustrates a cardiac assistdevice having muscle augmentation prior to defibrillation, in anepicardial position.

In yet another embodiment of the instant invention, the electrical leadmay be placed directly into a chamber of a heart, and in someembodiments, an atrium of the heart. The location of certain vulnerableplaque lesions may require that the electrical lead be placed directlyinto the heart. In such a case, positioning of the electrical lead maystill be obtained using the above surgical methods. Positioning the leadin the heart may indicate further treatment options, especially if theelectrical lead is placed into a ventricle. Placement into an atrium mayrequire fewer additional treatment options than placement of the leaddirectly into a ventricle. These treatment options, and the factors fortheir indication, are known to those of ordinary skill in the art.

After the electrical lead has been positioned adjacent a vulnerableplaque lesion, method 100 continues at block 120. At block 120, theelectrical lead is used to deliver at least one electrical pulse to thevulnerable plaque lesion. In one embodiment, the electrical leaddelivers the pulse after voltage is applied to the electrical lead.Other embodiments of the invention may deliver the electrical pulse byretracting a protective sheath from the lead. The lead may be anyappropriate electrical device, including electrodes. One lead that maybe appropriate for use is disclosed in U.S. Pat. No. 5,716,392, issuedFeb. 10, 1998 to Bourgeois et al. and assigned to the same assignee asthis application. The '392 patent discloses a minimally invasive medicalelectrical lead, as illustrated in FIG. 5 of the '392 patent.

The electrical pulse may be a high frequency, low voltage pulse. Thepulse may be delivered with a pulse generator for biomedicalapplications. Pulse generators for delivering a pulse of electricity toa body part are known in the art. One example of such a pulse generatoris described in the '379 patent, although any appropriate pulsegenerator may be used in practicing this invention. The frequency andvoltage are selected from ranges appropriate for cardiac treatment.

The electrical pulse may be applied for a specific time period. Thisperiod may be calculated to increase the thickness of the thin fibrouscap that covers vulnerable plaque lesions.

Subthreshold stimulation promotes production of angiogenic growthfactors with an electric field of 0.1 V/cm (Volts/centimeters) through1V/cm with a frequency from 10-100 Hertz (Hz). In a currently preferredembodiment, a field of 0.1 V/cm, at 50 Hz is applied for 0.1-3milliseconds.

Alternatively, a field with a current density of 60 microamperes/mm²lasting 10 milliseconds at a frequency of 10 Hz increases production ofthrombolytic peptides by the vascular endothelial cells. The amplitudeof this current may range from 0.1 V to 25 V (volts). When such a fieldis applied, the device applying the stimulation would include heartpacemaking capabilities 395 to pace the heart to facilitatesynchronization of the electrical current generation with the refractoryperiod of the heart. This field also promotes local accumulation ofcharged proteins and growth factors, moving the endothelial cells tomodulate cell proliferation and differentiation, stimulatingextra-cellular matrix production. These growth factors include VEGF,FGF, TGFBeta and BMP-2. Accumulation of the charged proteins and growthfactors thickens the fibrous cap.

Application of the high frequency, low voltage electrical pulse near thevulnerable plaque lesion may also have an anti-proliferative effect.Such an effect is characterized by reducing growth of a vulnerableplaque lesion. Although anti-proliferative effects do not eliminate thevulnerable plaque lesion, any adverse effects of the vulnerable plaquelesion may be reduced by reducing any growth of the lesion.

Application of the high frequency, low voltage electrical pulse near thevulnerable plaque lesion may also increase the thickness of the thinfibrous cap or covering that covers a lipid pool of the vulnerableplaque lesion. Such an effect may reduce the chances of a rupture of thethin fibrous cap, and may minimize the potentially adverse effects ofthe rupture.

FIG. 2 is a flow chart of a method of treating a vulnerable plaqueassociated with a blood vessel of a patient, in accordance with oneembodiment of the present invention. A vulnerable plaque isdistinguishable from other types of plaque, including hard plaques, bythe presence of a relatively thin fibrous cap. The vulnerable plaquefibrous cap retains a pool of lipids and other contents, which may bereleased into the blood vessel upon rupture of the cap. The releasedcontents and any resulting blood clots constitute emboli that can lodgein a blood vessel thereby posing a risk to the patient. Vulnerableplaques, unlike hard plaques, are generally non-occlusive and, as such,may not produce angina. The following description pertains to treatmentof these vulnerable plaques.

At block 210, a vulnerable plaque site is located. Several techniquesfor locating and detecting such lesions exist, and may include the useof imaging techniques. For example, X-rays may be used. In otherembodiments, more advanced imaging technologies may be applied,including tomographic scanning or magnetic resonance imaging.

Other methods of identifying vulnerable plaques have been proposed.These include sensing the temperature differential between healthyvascular tissue and the inflamed tissue of a vulnerable plaque. Devicesthat identify vulnerable plaques by the higher temperature of theinflamed tissue have been described in, for example, U.S. Pat. No.5,924,997 to Campbell and U.S. Pat. No. 6,475,159 to Casscells et al.

Detection techniques are described in detail above, and that discussionis equally applicable to an understanding of the embodiment of theinvention disclosed in FIG. 2.

At block 220, an electrical lead is positioned adjacent the vulnerableplaque lesion. After the lesion has been located, positioning theelectrical lead next requires accessing a target area. Numerous methodsmay used to access the target area. In some embodiments of theinvention, a catheter-based system will be used to position theelectrical lead. Catheter-based systems are well-known in the art, andgenerally comprise a catheter which is guided to the site using aguidewire. The catheter is slidably attached to the guidewire via alumen in the body of the catheter, such that the catheter surrounds theguidewire lumen, and slides along the guidewire. Such systems aregenerally monitored for accurate placement with imaging technologies,such as fluoroscopy, and may comprise the use of radio-opaque dyes.Catheter-based systems may include other devices as well, and mayinclude the detection means as described above.

Other delivery systems may also be used. In another embodiment of theinstant invention, the lead may be positioned through a thoracotomy. Ina thoracotomy, an opening is created in the thoracic area of a body. Useof a thoracotomy for positioning the lead may prove advantageous forpositioning the lead in certain positions within the thoracic region. Ina thoracotomy placement of the electrical lead, a thoracotomy is made toprovide access to the target area, and the electrical lead is placed inthe desired position after passing through the thoracotomy.

Another embodiment of the instant invention includes using alaparoscopic approach to positioning the electrical lead. Laparoscopy isa surgical technique that uses a series of smaller incisions, largeenough to allow insertion of a light, and appropriate surgical tools.Although laparoscopy is less invasive than a thoracotomy, it may notalways be preferred to use a laparoscopic approach. In a laparoscopicplacement of the electrical lead, appropriate incisions are made toprovide access to the target area, and the electrical lead is threadedthrough the incisions and placed in the desired position.

Yet another embodiment of the instant invention comprises the use ofopen surgical techniques to position the electrical lead. Although thisis perhaps the most invasive technique, it may be preferred for locatingthe electrical lead in certain positions.

The lead may be positioned at any appropriate location to deliver the atleast one electrical pulse. One embodiment comprises locating the leaddirectly within a blood vessel. Such an embodiment is likely to entailuse of a catheter-based system. The electrical lead may be placeddirectly in the blood vessel that comprises the vulnerable plaquelesion, such that no vessel wall is in the path of the electricalpulses. In another embodiment of the invention, the electrical lead maybe placed in a blood vessel that is not the same blood vessel thatcomprises the vulnerable plaque. In such an embodiment, at least twovessel walls will be in the path of the electrical pulse—the vessel wallcontaining the electrical lead, and the vessel wall comprising thevulnerable plaque lesion.

In another embodiment, the electrical lead is positioned epicardially.In an epicardial placement, the electrical lead is placed in anepicardial position, adjacent the heart. The placement may be in a bloodvessel, or may be positioned with a thoracotomy, laparoscopictechniques, or open surgical techniques. Placement of a differentelectrical device is disclosed in U.S. Pat. No. 5,716,379, issued Feb.10, 1998 to Bourgeois et. al, which is assigned to the same assignee asthis application. FIG. 1 of the '379 patent illustrates a cardiac assistdevice having muscle augmentation prior to defibrillation, in anepicardial position.

In yet another embodiment of the instant invention, the electrical leadmay be placed directly into a chamber of a heart, and in someembodiments, an atrium of the heart. The location of certain vulnerableplaque lesions may require that the electrical lead be placed directlyinto the heart. In such a case, positioning of the electrical lead maystill be obtained using the above surgical methods. Positioning the leadin the heart may indicate further treatment options, especially if theelectrical lead is placed into a ventricle. Placement into an atrium mayrequire fewer additional treatment options than placement of the leaddirectly into a ventricle. These treatment options, and the factors fortheir indication, are known to those of ordinary skill in the art.

After the electrical lead has been positioned adjacent a vulnerableplaque lesion, method 200 continues at block 230. At block 230, theelectrical lead is used to deliver at least one electrical pulse to thevulnerable plaque lesion. In one embodiment, the electrical leaddelivers the pulse after voltage is applied to the electrical lead.Other embodiments of the invention may deliver the electrical pulse byretracting a protective sheath from the lead. The lead may be anyappropriate electrical device, including electrodes. One lead that maybe appropriate for use is disclosed in U.S. Pat. No. 5,716,392, issuedFeb. 10, 1998 to Bourgeois et al. and assigned to the same assignee asthis application. The '392 patent discloses a minimally invasive medicalelectrical lead, as illustrated in FIG. 5 of the '392 patent.

The electrical pulse may be a high frequency, low voltage pulse. Thepulse may be delivered with a pulse generator for biomedicalapplications. Pulse generators for delivering a pulse of electricity toa body part are known in the art. One example of such a pulse generatoris described in the '379 patent, although any appropriate pulsegenerator may be used in practicing this invention. The frequency andvoltage are selected based on ranges appropriate for cardiac treatment.

Subthreshold stimulation promotes production of angiogenic growthfactors with an electric field of 0.1 V/cm (Volts/centimeters) through1V/cm with a frequency from 10-100 Hertz (Hz). In a currently preferredembodiment, a field of 0.1 V/cm, at 50 Hz is applied for 0.1-3milliseconds.

Alternatively, a field with a current density of 60 microamperes/mm²with a 10 millisecond duration and 10 Hz frequency increasesthrombolytic peptides by the vascular endothelial cells. The amplitudeof this current may range from 0.1 V to 25 V (volts). When such a fieldis applied, the device applying the stimulation would include heartpacemaking capabilities 395 to pace the heart to facilitatesynchronization of the electrical current generation with the refractoryperiod of the heart. This field also promotes local accumulation ofcharged proteins and growth factors, moving the endothelial cells tomodulate cell proliferation and differentiation, stimulatingextra-cellular matrix production. These growth factors include VEGF,FGF, TGFBeta and BMP-2. Accumulation of the charged proteins and growthfactors thickens the fibrous cap.

FIGS. 3A, 3B and 3C illustrate an electrical lead positioned adjacent avulnerable plaque lesion in accordance with embodiments of theinvention. In the embodiment illustrated in FIG. 3A, lead 325 ispositioned inside vessel 315 adjacent a vulnerable plaque lesion 330 invessel 315. Lead 325 is connected to an electricity source (not shown)with wire 305. FIG. 3B illustrates lead 325 positioned in theextravascular space, exterior to vessel 315, but still adjacent tovulnerable plaque lesion 330. FIG. 3C illustrates lead 325 positionedwithin a vessel 355 adjacent vessel 365 containing vulnerable plaquelesion 330. Vessel 355 may be a different region of vessel 365, orvessel 355 may be an entirely different vessel than vessel 355.

Those skilled in the art will recognize that although the presentinvention is described primarily in the context of treating a vulnerableplaque while using specific treatment devices, the inventor contemplatesa broader method of application. Any number of treatment devices capableof performing the prescribed function(s) may be compatible with thepresent invention. Furthermore, the treatment of the vulnerable plaqueis not limited to the described methodology. Numerous modifications,substitutions, and variations may be made to the method and system whileproviding effective vulnerable plaque treatment consistent with thepresent invention.

While the embodiments of the invention disclosed herein are presentlyconsidered preferred, various changes and modifications may be madewithout departing from the spirit and scope of the invention. Thesystem, device(s), and method of utilizing the same are not limited toany particular design or sequence. Specifically, the system and devicecomponents, procedure step order, and method of achieving the same mayvary without limiting the utility of the invention. Upon reading thespecification and reviewing the drawings hereof, it will becomeimmediately obvious to those skilled in the art that myriad otherembodiments of the present invention are possible, and that suchembodiments are contemplated and fall within the scope of the presentlyclaimed invention. The scope of the invention is indicated in theappended claims, and all changes that come within the meaning and rangeof equivalents are intended to be embraced therein.

1-16. (canceled)
 17. A method of treating vulnerable plaque, the methodcomprising: positioning an electrical lead adjacent a vulnerable plaquelesion in a vessel; and delivering at least one electrical pulse fromthe electrical lead to the vulnerable plaque lesion, the delivered pulseforming a field with a current density; and pacemaking a heart tosynchronize the delivered electrical pulse with a refractory period ofthe heart.
 18. The method of claim 17 wherein positioning the electricallead adjacent the vulnerable plaque lesion comprises delivering theelectrical lead through a vessel via a catheter.
 19. The method of claim18 wherein the vessel through which the electrical lead is delivered isadjacent the vessel having the lesion.
 20. The method of claim 18wherein the catheter is inserted in the vessel having the lesion. 21.The method of claim 17 wherein positioning the electrical lead adjacentthe vulnerable plaque lesion comprises delivering the electrical leadepicardially.
 22. The method of claim 17 wherein the at least oneelectrical pulse is a high frequency, low voltage pulse.
 23. The methodof claim 22 wherein the at least one electrical pulse has a frequency of50 Hertz and a voltage of 0.1 Volts/centimeter.
 24. The method of claim22 wherein the at least one electrical pulse has a frequency of 10Hertz, a voltage of 0.1 Volts/centimeter to 25 Volts/centimeter, and acurrent density of 60 microamperes/millimeter².
 25. The method of claim17 wherein positioning the electrical lead adjacent the vulnerableplaque comprises delivering through a thoracotomy.
 26. The method ofclaim 17 wherein positioning the electrical lead adjacent the vulnerableplaque comprises delivering through a laparoscope
 27. The method ofclaim 17 wherein positioning the electrical lead adjacent the vulnerableplaque comprises placing the electrical lead within a chamber of aheart.
 28. The method of claim 27 wherein the chamber of a heartcomprises an atrium.
 29. The method of claim 17 wherein the pulse isdelivered for a time period sufficient to thicken a fibrous cap of thelesion
 30. The method of claim 17 wherein the pulse is delivered for atime period sufficient to increase angiogenic growth.
 31. A system fortreating vulnerable plaque comprising: means for treating a vulnerableplaque lesion; and means for pacemaking a heart to synchronize thetreatment of the vulnerable plaque lesion with a refractory period ofthe heart.
 32. The system of claim 31 wherein the means for treating avulnerable plaque lesion comprises means for directing an electricalpulse toward a vulnerable plaque lesion, the at least one electricalpulse having a frequency of approximately 50 Hertz and a voltage ofapproximately 0.1 Volts/centimeter.
 33. The system of claim 32 whereinthe pulse is delivered for a time period sufficient to thicken a fibrouscap of the lesion
 34. A device for treating vulnerable plaquecomprising: means for directing an electrical pulse toward a vulnerableplaque lesion for a sufficient time period to increase capillary growthnear the vulnerable plaque; and means for pacemaking a heart tosynchronize the directed electrical pulse with a refractory period ofthe heart.